Molecular dynamics simulations of maltose in water

Abstract

The conformational preferences and flexibility of α-maltose were calculated using a modified GROMOS potential energy function. Six molecular dynamics (MD) simulations of α-maltose with explicit inclusion of water were run for up to 1000 ps each, starting from different conformations of the glycosidic linkage, the hydroxymethyl groups, and the hydroxyl groups. Comparison of calculated ensemble-averaged optical rotations with experimental data demonstrated an excellent agreement. Reasonable agreement was also found between experimental and calculated time-averaged NMR parameters. The global minimum centered at ϕ/ ψ 3 = −49°/−36° was populated to more than 90% of the time. The second minimum with ≈ 11 kJ/mol higher potential energy at ϕ/ ψ = − 29°/ − 173° represented the inverted conformation. Transitions between both minimum regions were only found from the local into the global minimum within the total simulation time of 5400 ps. The overall ratio between the staggered populations of the hydroxymethyl groups is gg: gt: tg = 70:23:6 for the reducing glucose, and gg: gt: tg = 55:38:6 for the nonreducing residue. Average lifetimes of the rotamers of the hydroxymethyl groups range between 5 ps for tg and 700 ps for gg conformers. The lowest energy barriers between the rotameric populations were estimated to be between 12 kJ/mol and 16 kJ/mol. Cluster analysis techniques employed to analyze the large amount of data in multidimensional space revealed correlations between the glycosidic linkage and the staggered forms of the hydroxymethyl groups. Interresidue hydrogen bonds that were found in less than 5% of all conformations occurred when the glycosidic linkage adopted conformations with relatively high ϕ and ψ values. Several additional minima that had been found from in vacuo studies are not stable once water is included since the importance of intramolecular hydrogen bonds is drastically reduced. Methodological aspects and the efficiency of MD simulations for reaching conformational equilibria are discussed.